scholarly journals Enhanced positive selection of a transgenic TCR by a restriction element that does not permit negative selection

1993 ◽  
Vol 5 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Pamela S. Ohashi ◽  
Rolf M. Zinkernagel ◽  
Immanuel Leuscher ◽  
Hans Hengartner ◽  
Hanspeter Pircher
Keyword(s):  
Positive Selection ◽  
Negative Selection ◽  
Restriction Element ◽  
Selection Of

scholarly journals Extreme C-terminal sites are posttranslocationally glycosylated by the STT3B isoform of the OST

2013 ◽  
Vol 201 (1) ◽  
pp. 81-95 ◽  
Author(s):  
Shiteshu Shrimal ◽  
Steven F. Trueman ◽  
Reid Gilmore
Keyword(s):  
Endoplasmic Reticulum ◽  
Positive Selection ◽  
Protein C ◽  
Negative Selection ◽  
Bioinformatics Analysis ◽  
Chain Termination ◽  
Catalytic Subunits ◽  
C Terminus ◽  
Glycosylation Sites ◽  
Selection Of

Metazoan organisms assemble two isoforms of the oligosaccharyltransferase (OST) that have different catalytic subunits (STT3A or STT3B) and partially nonoverlapping roles in asparagine-linked glycosylation. The STT3A isoform of the OST is primarily responsible for co-translational glycosylation of the nascent polypeptide as it enters the lumen of the endoplasmic reticulum. The C-terminal 65–75 residues of a glycoprotein will not contact the translocation channel–associated STT3A isoform of the OST complex before chain termination. Biosynthetic pulse labeling of five human glycoproteins showed that extreme C-terminal glycosylation sites were modified by an STT3B-dependent posttranslocational mechanism. The boundary for STT3B-dependent glycosylation of C-terminal sites was determined to fall between 50 and 55 residues from the C terminus of a protein. C-terminal NXT sites were glycosylated more rapidly and efficiently than C-terminal NXS sites. Bioinformatics analysis of glycopeptide databases from metazoan organisms revealed a lower density of C-terminal acceptor sites in glycoproteins because of reduced positive selection of NXT sites and negative selection of NXS sites.

scholarly journals Selection Pressures on RNA Sequences and Structures

2019 ◽  
Vol 15 ◽  
pp. 117693431987191 ◽  
Author(s):  
Katja Nowick ◽  
Maria Beatriz Walter Costa ◽  
Christian Höner zu Siederdissen ◽  
Peter F Stadler
Keyword(s):  
Positive Selection ◽  
Negative Selection ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Rna Sequences ◽  
Selection Pressures ◽  
Evolutionary Studies ◽  
Species Evolution ◽  
Selection Of

With the discovery of increasingly more functional noncoding RNAs (ncRNAs), it becomes eminent to more strongly consider them as important players during species evolution. Although tests for negative selection of ncRNAs already exist since the beginning of this century, the SSS-test is the first one for also investigating positive selection. When analyzing selection in ncRNAs, it should be taken into account that selection pressures can independently act on sequence and structure. We applied the SSS-test to explore the evolution of ncRNAs in primates and identified more than 100 long noncoding RNAs (lncRNAs) that might evolve under positive selection in humans. With this test, it is now possible to more thoroughly include ncRNAs into evolutionary studies.

scholarly journals B-Raf is required for positive selection and survival of DP cells, but not for negative selection of SP cells

2013 ◽  
Vol 25 (4) ◽  
pp. 259-269 ◽  
Author(s):  
Tara J. Dillon ◽  
Maho Takahashi ◽  
Yanping Li ◽  
Srilatha Tavisala ◽  
Susan E. Murray ◽  
...  
Keyword(s):  
Positive Selection ◽  
Negative Selection ◽  
Selection Of

CD8 is needed for positive selection but differentially required for negative selection of T cells during thymic ontogeny

1993 ◽  
Vol 23 (1) ◽  
pp. 212-216 ◽  
Author(s):  
Wai-Ping Fung-Leung ◽  
Valerie A. Wallace ◽  
Dawn Gray ◽  
William C. Sha ◽  
Hanspeter Pircher ◽  
...  
Keyword(s):  
T Cells ◽  
Positive Selection ◽  
Negative Selection ◽  
Selection Of

Promoter IV of the class II transactivator gene is essential for positive selection of CD4+ T cells

Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3550-3559 ◽  
Author(s):  
Jean-Marc Waldburger ◽  
Simona Rossi ◽  
Georg A. Hollander ◽  
Hans-Reimer Rodewald ◽  
Walter Reith ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Epithelial Cells ◽  
Positive Selection ◽  
Negative Selection ◽  
Cd4 T Cell ◽  
Thymic Epithelial Cells ◽  
Mhcii Expression ◽  
Selection Of

Major histocompatibility complex class II (MHCII) expression is regulated by the transcriptional coactivator CIITA. Positive selection of CD4+ T cells is abrogated in mice lacking one of the promoters (pIV) of the Mhc2ta gene. This is entirely due to the absence of MHCII expression in thymic epithelia, as demonstrated by bone marrow transfer experiments between wild-type and pIV−/− mice. Medullary thymic epithelial cells (mTECs) are also MHCII− in pIV−/− mice. Bone marrow–derived, professional antigen-presenting cells (APCs) retain normal MHCII expression in pIV−/− mice, including those believed to mediate negative selection in the thymic medulla. Endogenous retroviruses thus retain their ability to sustain negative selection of the residual CD4+ thymocytes in pIV−/− mice. Interestingly, the passive acquisition of MHCII molecules by thymocytes is abrogated in pIV−/−mice. This identifies thymic epithelial cells as the source of this passive transfer. In peripheral lymphoid organs, the CD4+T-cell population of pIV−/− mice is quantitatively and qualitatively comparable to that of MHCII-deficient mice. It comprises a high proportion of CD1-restricted natural killer T cells, which results in a bias of the Vβ repertoire of the residual CD4+ T-cell population. We have also addressed the identity of the signal that sustains pIV expression in cortical epithelia. We found that the Jak/STAT pathways activated by the common γ chain (CD132) or common β chain (CDw131) cytokine receptors are not required for MHCII expression in thymic cortical epithelia.

scholarly journals T cell receptor-mediated signaling events in CD4+CD8+ thymocytes undergoing thymic selection: requirement of calcineurin activation for thymic positive selection but not negative selection.

1995 ◽  
Vol 181 (3) ◽  
pp. 927-941 ◽  
Author(s):  
C R Wang ◽  
K Hashimoto ◽  
S Kubo ◽  
T Yokochi ◽  
M Kubo ◽  
...  
Keyword(s):  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
Intracellular Signaling ◽  
Negative Selection ◽  
Cell Receptor ◽  
Clonal Deletion ◽  
Signaling Events ◽  
Selection Of

The goal of this study was to identify the differences of intracellular signals between the processes of thymic positive and negative selection. The activation of calcineurin, a calcium- and calmodulin-dependent phosphatase, is known to be an essential event in T cell activation via the T cell receptor (TCR). The effect of FK506, an inhibitor of calcineurin activation, on positive and negative selection in CD4+CD8+ double positive (DP) thymocytes was examined in normal mice and in a TCR transgenic mouse model. In vivo FK506 treatment blocked the generation of mature TCRhighCD4+CD8- and TCRhighCD4-CD8+ thymocytes, and the induction of CD69 expression on DP thymocytes. In addition, the shutdown of recombination activating gene 1 (RAG-1) transcription and the downregulation of CD4 and CD8 expression were inhibited by FK506 treatment suggesting that the activation of calcineurin is required for the first step (or the very early intracellular signaling events) of TCR-mediated positive selection of DP thymocytes. In contrast, FK506-sensitive calcineurin activation did not appear to be required for negative selection based on the observations that negative selection of TCR alpha beta T cells in the H-2b male thymus (a negative selecting environment) was not inhibited by in vivo treatment with FK506 and that there was no rescue of the endogenous superantigen-mediated clonal deletion of V beta 6 and V beta 11 thymocytes in FK506-treated CBA/J mice. DNA fragmentation induced by TCR activation of DP thymocytes in vitro was not affected by FK506. In addition, different effects of FK506 from Cyclosporin A on the T cell development in the thymus were demonstrated. The results of this study suggest that different signaling pathways work in positive and negative selection and that there is a differential dependence on calcineurin activation in the selection processes.

scholarly journals The T cell receptor repertoire of CD4-8+ thymocytes is altered by overexpression of the BCL-2 protooncogene in the thymus.

1994 ◽  
Vol 179 (1) ◽  
pp. 145-153 ◽  
Author(s):  
W Tao ◽  
S J Teh ◽  
I Melhado ◽  
F Jirik ◽  
S J Korsmeyer ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Transgenic Mice ◽  
Positive Selection ◽  
T Cell Receptor ◽  
Negative Selection ◽  
Cell Receptor ◽  
Target Cells ◽  
Cell Death Pathway ◽  
Selection Of

The bcl-2 gene encodes an intracellular, membrane-associated protein that protects immature cortical thymocytes from a wide variety of apoptotic stimuli, including glucocorticoids, radiation, and anti-CD3 treatment. Since cortical thymocytes are the primary target cells for thymic positive and negative selection processes, and since these processes are associated with cell death, we evaluated the role of bcl-2 in T cell development in two ways. In the first approach, transgenic mice expressing high levels of Bcl-2 in cortical thymocytes were mated with H-Y T cell receptor (TCR) transgenic mice, the latter being a well-defined system for the study of positive and negative selection of T cells. We found that the bcl-2 transgene had a dramatic effect on positive selection. This was manifested by a greatly increased production of mature thymocytes that were highly skewed towards the CD4-8+ lineage. The change involving CD4-8+ thymocytes occurred not only in bcl-2 transgenic mice, but was also observed in H-Y TCR/bcl-2 doubly transgenic mice, regardless of whether the H-Y TCR was expressed in the selecting (H-2b) or nonselecting (H-2d) environments. Furthermore, a large proportion of CD4-8+ thymocytes produced in H-2b H-Y TCR/bcl-2 doubly transgenic female mice expressed endogenous TCR alpha chains rather than the transgenic TCR alpha chain. These observations are consistent with the model that high expression of Bcl-2 in cortical thymocytes overrides the normal apoptotic pathway. This then allows the selection of CD4-8+ thymocytes expressing TCRs that are otherwise nonselectable. However, the bcl-2 transgene did not protect CD4+8+ thymocytes expressing the male-specific TCR from deletion in male doubly transgenic mice. In the second approach, we determined the level of bcl-2 mRNA expression in populations of thymocytes defined by their CD4/CD8 phenotypes using quantitative reversed transcriptase PCR techniques. Our results indicate that bcl-2 mRNA was expressed at a high level in immature CD4-8- thymocytes and in mature CD4+8- thymocytes. There is a dramatic downregulation of bcl-2 mRNA in CD4+8+ thymocytes, particularly those expressing a low level of TCR. CD4+8+ thymocytes that upregulated their TCR, likely as a result of receiving positive selection signals, also upregulated bcl-2 mRNA. This observation suggests that rescue of immature thymocytes from the programmed cell death pathway by positive selection signals is accompanied by the upregulation of bcl-2 mRNA.

scholarly journals Absence of H-2 restriction in primary and secondary mixed-lymphocyte reactions to strong M1s determinants.

1980 ◽  
Vol 151 (2) ◽  
pp. 407-417 ◽  
Author(s):  
K Molnar-Kimber ◽  
J Sprent
Keyword(s):  
T Cells ◽  
Positive Selection ◽  
Proliferative Response ◽  
Negative Selection ◽  
Selection Procedures ◽  
Per Se ◽  
Mixed Lymphocyte Reactions ◽  
Selection Of

Negative and positive selection procedures were used to establish whether the strong proliferative response of T cells to M1sa determinants is H-2 restricted. After negative selection of H-2 determinants in vivo, it was shown that T cells give high primary mixed lymphocyte reactions in vitro to M1sa determinants presented on H-2-incompatible stimulator cells. Other studies demonstrated that (a) negative selection of T cells to M1sa determinants on H-2-incompatible cells removed T cells with specificity for M1sa-bearing H-2-compatible cells, and (b) T cells primed in vitro or in vivo to M1sa determinants on H-2-compatible cells gave high secondary responses to M1sa determinants presented either on H-2-compatible or H-2-incompatible stimulator cells. From these data we conclude that T cells recognize M1sa determinants per se rather than an association of M1sa plus self or allo-H-2 determinants.

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